AB0082 AGE-RELATED GENES USP2 AND ARG2 ARE INVOLVED IN THE REDUCTION OF IMMUNE CELL INFILTRATION IN ELDERLY PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Q. Cheng, Y. Du, H. Wu
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> As the prevalence of rheumatoid arthritis (RA) in the elderly is increasing, rheumatologists are increasingly concerned about this group of patients. There is a large gap between the clinical manifestations and biological markers of elderly patients with RA (EPRA, age &gt; 60) and younger patients with RA (YPRA, age ≤ 60), in part from the differences in the immune system in different age groups. The current understanding of EPRA remains insufficient. <h3>Objectives</h3> For better understanding of the mechanism of RA disease progression and subsequent treatment options, here we focused on the changes of immune cell infiltration in YPRA and EPRA. <h3>Methods</h3> R package "ssGSEA" and "GSEA" were used to identify the changes in immune cell infiltration and immune-related pathways. R package "WGCNA" and "DEseq2" were used to screening and verifying age-related differentially expressed genes (DEGs). Hub genes were identified by Cytoscape and cytoHubba. ROC (receiver operator characteristic) analysis was performed to determine the prediction and value of biomarkers. Spearman correlation analysis was conducted to evaluate the correlation between hub age-related genes and immune cells. <h3>Results</h3> In early RA patients (defined as within 12 months of onset of symptoms), there were no differences in the infiltration of 28 types of immune cells between younger and older patients. However, in established RA patients, several immune cells were markedly decreased in older patients, including activated B cells, immature B cells, natural killer cells, CD56dim natural killer cells, MDSCs, monocytes, effector memory CD8+T cells, regulatory T cells, type 1 T helper cells, type 17 T helper cells and T follicular helper cells. Moreover, 78 age-related DEGs related to amino acid and glycosphingolipid synthesis and metabolism were identified by WGCNA analysis and DEG screening. AGMAT, ARG2, OMG, USP2, IL4I1, and ISG15 were obtained by construction of molecular interaction regulatory networks. After verification by GEO validation set and our own RA synovial samples, only two genes, USP2 and ARG2, were still upregulated in EPRA after verification (Figure 1) and ARG2 and USP2 could effectively distinguish YPRA and EPRA and had potential as biomarkers. <h3>Conclusion</h3> In conclusion, this study is the first to systematically analyze changes in immune cell infiltration between younger and older RA patients and obtain hub age-related genes, which may provide the basis for illuminating the pathogenesis of RA and informing treatment strategies. <h3>References</h3> [1]Safiri S, Kolahi AA, Hoy D, Smith E, Bettampadi D, Mansournia MA<i>, et al.</i> (2019). Global, regional and national burden of rheumatoid arthritis 1990-2017: a systematic analysis of the Global Burden of Disease study 2017. Ann Rheum Dis, 78:1463-1471. [2]Serhal L, Lwin MN, Holroyd C, Edwards CJ (2020). Rheumatoid arthritis in the elderly: Characteristics and treatment considerations. Autoimmun Rev, 19:102528. [3]Rasch EK, Hirsch R, Paulose-Ram R, Hochberg MC (2003). Prevalence of rheumatoid arthritis in persons 60 years of age and older in the United States: effect of different methods of case classification. Arthritis Rheum, 48:917-926. [4]Chalan P, van den Berg A, Kroesen BJ, Brouwer L, Boots A (2015). Rheumatoid Arthritis, Immunosenescence and the Hallmarks of Aging. Curr Aging Sci, 8:131-146. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.